Dopamine elevates and lowers astroglial Ca²⁺ through distinct pathways depending on local synaptic circuitry

Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca²⁺ rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca²⁺ in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca²⁺ ] measurements, we also employed life-time imaging of the Ca²⁺ indicator Oregon Green BAPTA-1. We found that dopamine triggered a dose-dependent, bidirectional Ca²⁺ response in stratum radiatum astroglia, a jagged elevation accompanied and followed by below-baseline decreases. The elevation depended on D1/D2 receptors and engaged intracellular Ca²⁺ storage and removal whereas the dopamine-induced [Ca²⁺ ] decrease involved D2 receptors only and was sensitive to Ca²⁺ channel blockade. In contrast, the stratum lacunosum moleculare astroglia generated higher-threshold dopamine-induced Ca²⁺ responses which did not depend on dopamine receptors and were uncoupled from the prominent inhibitory action of dopamine on local perforant path synapses. Our findings thus suggest that a single neurotransmitter-dopamine-could either elevate or decrease astrocyte [Ca²⁺ ] depending on the receptors involved, that such actions are specific to the regional neural circuitry and that they may be causally uncoupled from dopamine actions on local synapses. The results also indicate that [Ca²⁺ ] elevations commonly detected in astroglia can represent the variety of distinct mechanisms acting on the microscopic scale. GLIA 2017;65:447-459.